Enol Content and Enolization

Writing the bromine addition step in this way emphasizes the increased nucleophilicity of the enol double bond and identifies the source of that increased nucleophilicity as the enolic oxygen. 

PROBLEM 18.4 Represent the reaction of chlorine with each of the enol forms of 2-butanone (see Problem 18.3) according to the curved arrow formalism just described. 

The cationic intermediate is simply the protonated form (conjugate acid) of the a-halo ketone. Deprotonation of the cationic intermediate gives the products. 

Having now seen how an enol, once formed, reacts with a halogen, let us consider the process of enolization itself. 

Enols are related to an aldehyde or a ketone by a proton-transfer equilibrium known as keto-enol tautomerism. (Tautomerism refers to an interconversion between two structures that differ by the placement of an atom or a group.) 

You have had earlier experience with enols in their role as intermediates in the hydration of aUcynes (Section 9.12). The mechanism of enolization of aldehydes and ketones is precisely the reverse of the mechanism by which an enol is converted to a carbonyl compound. 

Is the product a mixture of enantiomers or diastereomers Is the reaction enantioselective or diastereoselective  

To complete the synthesis, the major and minor products were separated, and the major stereoisomer hydrolyzed (nucleophilic acyl substitution) to give the desired enantiomer-ically pure (5 )-2-methyl-4-pentenoic acid. 

The other product of hydrolysis is the original chiral auxiliary it is recovered to be used another day. 

The kind of sequence described here is often termed an asymmetric synthesis, the stereoselective introduction of a chirality center in a reactant in which the stereoisomeric products are formed in unequal amounts. 

As Sections 20.3 through 20.12 demonstrate, the importance of enolates in organic chemistry lies in their synthetic applications, especially in procedures involving the formation of carbon-carbon bonds. What about enols—the conjugate acids of enolates  

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Aldehyde, Ketone, and Ester Enolates 867 Enolate Regiochemistry 872 The Aldol Condensation 873 Mixed Aldol Condensations 878 Chalcones From the Mulberry Tree to Cancer Chemotherapy 880 The Claisen Condensation 882 Intramolecular Claisen Condensation The Dieckmann Cyclization 884 Mixed Claisen Condensations 885 Acylation of Ketones with Esters 886 Alkylation of Enolates 887 The Acetoacetic Ester Synthesis 889 The Malonic Ester Synthesis 891 Alkylation of Chiral Enolates 893 Enolization and Enol Content 895 a Halogenation of Aldehydes and Ketones 900... 

The former exhibits absorption tjrpical of an isolated keto group, whereas the latter shows a high intensity -band associated with the conjugated system HO—C=C—C=0. The proportions of the two forms under various conditions are readily determined from the ultraviolet spectra. The ultraviolet spectra in various solvents are shown in Fig. A, 7, 2. Since the absorption of the keto form is negligible, the percentage of enol present is 100(em/e ), where e is the observed extinction at 245 mp. and that of the pure enol. It was shown that in alcoholic solution is 1900 and the percentage of enol is 12. Thus e is ca. 16000, and use of this value permits the approximate evaluation of the enol content in different solvents. The results are collected in Table XII. 

The amount of enol present at equilibrium the enol content is quite small for sim pie aldehydes and ketones The equilibrium constants for enolization as shown by the following examples are much less than 1... 

Enolization (Sections 18 4 through 18 6) Aldehydes and ke tones having at least one a hydro gen exist in equilibrium with their enol forms The rate at which equilibrium is achieved is in creased by acidic or basic cata lysts The enol content of simple aldehydes and ketones is quite small p diketones however are extensively enolized... 

The enol content of a carboxylic acid is far less than that of an aldehyde or ketone and introduction of a halogen substituent at the a carbon atom requires a different set... 

The chemical properties of cycHc ketones also vary with ring size. Lower members (addition reactions, than corresponding acycHc ketones. The Cg—C 2 ketones are unreactive, reflecting the strain and high enol content of medium-sized ring systems. Lactones are prepared from cycHc ketones by the Bayer-ViUiger oxidation reaction with peracids. S-Caprolactone is manufactured from cyclohexane by this process ... 

In each of the following pairs of compounds, choose the one that has the greater enol content, and write the structure of its enol form ... 

Unlike most /3-diketones, the following /3-diketone has no detectable enol content and is about as acidic as acetone. Explain. 

The liquid ester is an equilibrium mixture, the enol content of which is increased by distillation and falls slowly, on standing, to 30 per cent.1 The boiling point of i45-i47°/n mm., recorded in the literature, is higher than any noted in the present work. 

Frequently, when the enol content is high, both forms can be isolated. The pure keto form of acetoacetic ester melts at — 39°C, while the enol is a liquid even at — 78°C. Each can be kept at room temperature for days if catalysts such as acids or bases are rigorously excluded.Even the simplest enol, vinyl alcohol (CH2= CHOH), has been prepared in the gas phase at room temperature, where it has a half-life of 30min. " The enol Me2C=CCHOH is indefinitely stable in the solid state at —78°C and has a half-life of 24h in the liquid state at 25°C. When both forms cannot be isolated, the extent of enolization is often measured by NMR. 

The enol content of the product at this point is less than 2%. If the unenolized enedione is desired, the following distillation should be omitted and the product used without purification to avoid further isomerization. 

The method detailed here uses cheap starting materials and the sequence proceeds in high-yielding steps. Finally, it is noted that the title compound can exhibit high enol content depending on solvent.2... 

The earliest estimates of the enol content of various p-diketones was made by careful distillation (Meyer and Schoeller, 1920 Meyer and Hopflf, 1921). Although, as a method of studying the equilibrium, this approach has been replaced by non-intrusive methods, work on the physical separation of the tautomers has continued (e.g. Regitzand Schafer, 1981 Vogt and Gompper, 1981). 

Traditionally, the position of equilibrium of (15) has been expressed as the percentage of enol, and for neat pentane-2,4-dione this is 79%. The equilibrium constant is especially sensitive to solvents for pentane-2,4-dione the enol content varies from 13% in water to 98% in cyclohexane, corresponding to a ca. 300-fold change in the value of the equilibrium constant. 

Rate and equilibrium constant measurements for the enolization of 3-phenylcoumaran-2-one (82) in aqueous dioxane indicate an enol content of ca 0.1%, a pKg, of 8.9 (6.0 for the enol tautomer), and a fairly symmetrical transition state for enolate anion formation the Brpnsted Pb = 0.52 Below pH 5, enolization is independent of pH, occurring via O-protonation of the enolate. 

Ness, A. B., and S. M. McElvain The Enol Content of Some /S-Keto Esters. 

Since fluoro-carbonyl compounds are such useful and versatile synthetic intermediates, much effort has been devoted to their preparation [124], but only in a few instances has elemental fluorine been used directly. One of the earliest successful direct fluorinations of a simple carbonyl compound was the fluorina-tion of pyruvic acid derivatives which have a high enol content (R = Aryl, Acyl) (Fig. 47) [125] in the solvent being used (mixtures of CF2C1CFC12 and acetonitrile). However, in derivatives where the enol content was low (R = Alkyl), complicated mixtures of products were obtained. 

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